HVint: A Strategy for Identifying Novel Protein-Protein Interactions in Herpes Simplex Virus Type 1.
HVint: A Strategy for Identifying Novel Protein-Protein Interactions in Herpes Simplex Virus Type 1.
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DOI：
10.1074/mcp.m116.058552
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发表时间：
2016-09
期刊：
影响因子：
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通讯作者：
Topf M
中科院分区：
文献类型：
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作者：
Ashford P;Hernandez A;Greco TM;Buch A;Sodeik B;Cristea IM;Grünewald K;Shepherd A;Topf M
人类疱疹病毒是广泛分布的人类病原体，对全球公共卫生产生显著影响。尽管几十年来进行了深入的研究，但其功能的许多方面的分子细节仍有待充分表征。要解开这些病毒如何运作的细节，彻底了解所涉及的组件之间的关系是关键。在这里，我们提出了HVint，一种新的蛋白质-蛋白质病毒内相互作用资源的单纯疱疹病毒1型（HSV-1）整合数据从五个外部来源。为了评估每种相互作用，我们使用了一种评分方案，该方案考虑了检测方法的类型和证据线的数量等方面。最初的相互作用组的覆盖范围进一步增加使用进化信息，通过进口的相互作用报告的其他人类疱疹病毒。这些后者的相互作用构成，因此，HSV-1中潜在的新的相互作用的计算预测。进行了独立的实验分析，以确认我们预测的相互作用的子集。该亚组涵盖了有助于核出口和初级增殖事件的蛋白质，包括VP 26、pUL 31、pUL 40和最近表征的pUL 32和pUL 21。我们的研究结果支持VP 26和蛋白质如pUL 31，pUS 9和CSVC复合物之间的协调串扰，有助于描述新合成的HSV-1衣壳的核出口和主要增殖途径的模型的发展。该结果也与最近关于pUL 32参与衣壳成熟和早期盖化事件的发现一致。此外，它们为pUS 9依赖性运输的病毒特异性调节剂的新假设打开了大门。为了使科学界能够轻松访问这个交互存储库，我们还开发了一个用户友好且交互式的网络界面。我们的方法展示了计算预测的力量，以帮助设计有针对性的实验，发现新的蛋白质-蛋白质相互作用。
Human herpesviruses are widespread human pathogens with a remarkable impact on worldwide public health. Despite intense decades of research, the molecular details in many aspects of their function remain to be fully characterized. To unravel the details of how these viruses operate, a thorough understanding of the relationships between the involved components is key. Here, we present HVint, a novel protein-protein intraviral interaction resource for herpes simplex virus type 1 (HSV-1) integrating data from five external sources. To assess each interaction, we used a scoring scheme that takes into consideration aspects such as the type of detection method and the number of lines of evidence. The coverage of the initial interactome was further increased using evolutionary information, by importing interactions reported for other human herpesviruses. These latter interactions constitute, therefore, computational predictions for potential novel interactions in HSV-1. An independent experimental analysis was performed to confirm a subset of our predicted interactions. This subset covers proteins that contribute to nuclear egress and primary envelopment events, including VP26, pUL31, pUL40, and the recently characterized pUL32 and pUL21. Our findings support a coordinated crosstalk between VP26 and proteins such as pUL31, pUS9, and the CSVC complex, contributing to the development of a model describing the nuclear egress and primary envelopment pathways of newly synthesized HSV-1 capsids. The results are also consistent with recent findings on the involvement of pUL32 in capsid maturation and early tegumentation events. Further, they open the door to new hypotheses on virus-specific regulators of pUS9-dependent transport. To make this repository of interactions readily accessible for the scientific community, we also developed a user-friendly and interactive web interface. Our approach demonstrates the power of computational predictions to assist in the design of targeted experiments for the discovery of novel protein-protein interactions.
影响因子：
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作者：
Marras E;Travaglione A;Chaurasia G;Futschik M;Capobianco E
通讯作者：
Capobianco E